The enthalpy (ΔH) and structural volume changes (ΔV) associated with the formation and decay of the early intermediate K₆₀₀ in the photocycle of Natronobacterium pharaonis halorhodopsin (pHR), an inward-directed anion pump, were obtained by laser-induced optoacoustic spectroscopy. A large expansion is associated with K₆₀₀ formation, its value depending on the medium and on the anion (Cl⁻, NO₃⁻, Br⁻, I⁻). A smaller expansion is associated with K₆₀₀ decay to L₅₂₀. A contraction is found for the same step in the case of the azide-loaded pHR which is an efficient outward-directed proton pump. Thus, the conformational changes in L₅₂₀ determine the direction and sign of charge translocation. The linear correlation between ΔH and ΔV for chloride-loaded pHR observed upon mild medium variations is attributed to enthalpy–entropy compensation effects and allows the calculation of the free-energy changes, ΔG_K = (97 ± 16) kJ/mol and ΔG_KL = −(2 ± 2) kJ/mol. Different from other systems, ΔS correlates negatively with ΔV in the first steps of the pHR photocycle. Thus, the space around the anion becomes larger and more rigid during each of these two steps. The photocycle quantum yield was 0.52 for chloride-pHR as measured by laser flash photolysis.